Abstracts (complete list) - Wissenschaft Online

Elke Scandella, Evelyn Lattmann, Sanjiv Luther, Simone Miller, Tobias Junt, Burkhard
Ludewig
Role for lymphoid tissue inducer-like cells in the restoration
of immunopathological destruction of the lymphoid stroma
cell network
Many viral infections, including human Hepatitis B and C or immunodeficiency viruses
(HIV) are associated with an immunopathological damage of secondary lymphoid
organs leading to immunosupression. Similarly, infection of mice with the lymphocytic
choriomengitis virus (LCMV) leads to destruction of secondary lymphoid organ structure
which is mediated by virus-specific cytotoxic T cells (CTL). In this study we show that
the destruction also affects follicular dendritic cells and gp38+ T zone stroma cells which
are the major producers of the constitutive chemokines CXCL13, CCL19 and CCL21b
and are therefore essential for the maintenance of lymphoid structures. Furthermore,
LCMV infected gp38+ stroma cells were lysed by activated virus-specific CTL. The loss
of stroma cell network is corroborated by a transient reduction of constitutive
chemokines. A gene-array analysis revealed that genes which are crucial for the
development of lymphoid organs, e.g. lymphotoxin-b, IL-7Ra or VCAM-1, were upregulated
concomitantly, thus indicating the immediate initiation of a transcriptional
'reorganization program'. Moreover, we found accumulation and proliferation of CD3-
CD4+IL7-Ralpha+ positive cells, which phenotypically resemble lymphoid tissue inducer
(LTi) cells and are required for lymphoid organ development. In addition, mice lacking
LTi cells display a delay in the re-expression of CCL19, CCL21 and CXCL13 following
LCMV infection.